LDL-APHERESIS IS A TREATMENT OPTION FOR PATIENTS WITH SEVERE HYPERCHOLESTEROLEMIA AND CORONARY ARTERY DISEASE, WHICH REDUCES ELEVATED LDL-CHOLESTEROL LEVELS TO NEAR NORMAL RANGE. IT IS UNKNOWN, HOWEVER, WHETHER SUCH THERAPY CHANGES ENDOGENOUS KINETIC PARAMETERS OF LIPOPROTEIN METABOLISM, SUCH AS APOLIPOPROTEIN B (APOB) SECRETION RATES (SR), CONVERSION RATES (CR), AND FRACTIONAL CATABOLIC RATES (FCR) WHICH COULD COUNTERACT THE BENEFICIAL EFFECT OF APHERESIS. WE STUDIED METABOLIC PARAMETERS OF APOB IN 3 MALE FAMILIAL HYPERCHOLESTEROLEMIA (FH) HETEROZYGOTES (AGE 4318 YRS, BMI 28.914.8 KG.M-2) USING ENDOGENOUS LABELING WITH D3-LEUCINE, MASS SPECTROMETRY AND MULTICOMPARTMENTAL MODELING. PATIENTS WERE STUDIED PRIOR TO AND FOLLOWING 3-6 MONTHS OF APHERESIS THERAPY. THE SECOND METABOLIC STUDY WAS PERFORMED 7 DAYS AFTER WEEKLY APHERESIS. PATIENTS WERE OFF HYPOLIPIDEMIC DRUGS, AND CONCOMITANT MEDICATIONS AND DIETS REMAINED UNCHANGED. PRIOR TO APHERESIS THERAPY PLASMA APOB CONCENTRATION (MG.DL-1) WAS 239128; THIS DECREASED (P<0.05) TO 65.5111.3 IMMEDIATELY AFTER APHERESIS AND 179.019.9 BEFORE THE NEXT APHERESIS. VLDL-APOB FCR (D-1) WAS 4.3511.7 AND 3.111.8 (NS) AND LDL-APOB FCR (D-1) WAS 0.1610.07 AND 0.1610.11 (NS) BEFORE AND DURING APHERESIS RESPECTIVELY. NEITHER APOB SR (14.717.6 VS. 11.718.6 MG.KG1.D-1) NOR VLDL TO LDL-APOB CR (86.919.1 VS. 83.2113.2 %) CHANGED WITH THERAPY. WE CONCLUDE THAT IN THIS STUDY APHERESIS THERAPY DOES NOT ALTER APOB METABOLIC PARAMETERS IN FH HETEROZYGOTES AND THAT THE BENEFICIAL EFFECT OF APHERESIS THERAPY IS NOT COUNTERACTED BY CHANGES IN APOB PRODUCTION OR CATABOLISM.